Vitamin C could hasten TB cure

Vitamin-C, known for its numerous health benefits now gets another
feather in its cap, with new research suggesting that when taken with tuberculosis
(TB) drugs, the vitamin could help cure the disease in lesser time than standard
treatment methods1.

Researchers, led by Jaya Sivaswami Tyagi, at the
biotechnology department of the All India Institute of Medical Sciences (AIIMS)
in New Delhi, have used ‘network-based gene expression analysis’ to show that vitamin-C
"triggers a multifaceted and robust adaptation response in the TB-causing
bacteria Mycobacterium tuberculosis (Mtb).”

Standard treatment regimens take six months or more to cure
TB. One reason for this is a subpopulation of Mtb that uses a clever survival
strategy to trick the drugs that target actively replicating bacteria. This
subpopulation enters into a dormant state where it does not divide, thus
evading drug action, but is still latently alive and can flare up into active
disease anytime.

"Therefore, a major research priority of TB scientists
has been to decode the critical survival pathways in dormant tubercle bacilli
in order to formulate new approaches for killing these bacteria," Tyagi,
told Nature India.

India has the largest number of TB cases in the world at 23%
of the global total and bacterial dormancy has been a major impediment to the
eradication of the disease.

"When we investigated drug combinations used to treat
patients, we found that the four-drug combination – which has pyrazinamide
(PZA) plus added vitamin C – could efficiently kill the subpopulations
including the tricky dormant bacteria," Tyagi said.

Although vitamin-C is not itself an antibacterial, it synergizes
with PZA, a key first line TB drug, to kill dormant and replicating bacteria,
negating their tolerance to TB drugs – rifampicin and isoniazid – in
combination treatment.

These findings suggest a novel strategy of using vitamin- C
as an adjunct to existing drugs to modulate the physiology of tubercle bacilli
for enhanced efficacy of combination chemotherapy, the researchers report. They
say that Vitamin C-based models can also be used as novel "screening
platforms" to test new drugs and drug combinations for accelerating TB
treatment.

"The authors have studied detailed mechanisms how
Vitamin-C can be an effective and cheap addition to TB therapy," Vikram
Saini, microbiologist at the University of Alabama at Birmingham told Nature India. "It has created
substantial interest in the US and I believe it will be a very relevant study
in the Indian context."

According to the researchers, the effects of vitamin-C in
combination treatment were reproduced in an intra-cellular model, more akin to
human infection." Based on these findings, we propose a new strategy
involving vitamin- C as an adjunctive treatment agent,” the researchers
advocate.